Prior studies have suggested that insulin may play an important role in the regulation of pancreatic acinar cell metabolism. Preliminary studies by the principal investigators have demonstrated the presence of specific binding sites for insulin on isolated pancreatic acini and that after binding insulin stimulates glucose transport. It is proposed that the binding of insulin and stimulation of membrane transport and enzyme synthesis plus secretion will be studied in pancreatic pieces, isolated acini and cultured cells from both normal and diabetic animals. The localization of specific insulin binding sites will be measured by both direct binding sites and autoradiographs in isolated acini and purified subcellular fractions. The effects of insulin on enzyme release will be studied as to whether the hormone has an effect on calcium mediated stimulus-secretion coupling. Effects of insulin on amylase synthesis will be measured using incorporation of radioactive amino acids and immunoprecipitation. Effects of insulin on the transport of glucose, amino acids and ions will be measured with respect to whether the effects of insulin on amylase synthesis and secretion are direct or secondary to altered metabolism. These studies should define the role of insulin in regulating pancreatic exocrine function and may provide a model cell system for studying both long- and short-term cellular effects of insulin.